Screening for medium chain acyl-CoA dehydrogenase deficiency using electrospray ionisation tandem mass spectrometry

OBJECTIVE: To establish criteria for the diagnosis of medium chain acyl-CoA dehydrogenase (MCAD) deficiency in the UK population using a method in which carnitine species eluted from blood spots are butylated and analysed by electrospray ionisation tandem mass spectrometry (ESI-MS/MS). DESIGN: Four groups were studied: (1) 35 children, aged 4 days to 16.2 years, with proven MCAD deficiency (mostly homozygous for the A985G mutation, none receiving carnitine supplements); (2) 2168 control children; (3) 482 neonates; and (4) 15 MCAD heterozygotes. RESULTS: All patients with MCAD deficiency had an octanoylcarnitine concentration ([C8-Cn]) > 0.38 microM and no accumulation of carnitine species > C10 or < C6. Among the patients with MCAD deficiency, the [C8-Cn] was significantly lower in children > 10 weeks old and in children with carnitine depletion (free carnitine < 20 microM). Neonatal blood spots from patients with MCAD deficiency had a [C8-Cn] > 1.5 microM, whereas in heterozygotes and other normal neonates the [C8-Cn] was < 1.0 microM. In contrast, the blood spot [C8-Cn] in eight of 27 patients with MCAD deficiency > 10 weeks old fell within the same range as five of 15 MCAD heterozygotes (0.38-1.0 microM). However, the free carnitine concentrations were reduced (< 20 microM) in the patients with MCAD deficiency but normal in the heterozygotes. CONCLUSIONS: Criteria for the diagnosis of MCAD deficiency using ESI-MS/MS must take account of age and carnitine depletion. If screening is undertaken at 7-10 days, the number of false positive and negative results should be negligible. Because there have been no instances of death or neurological damage following diagnosis of MCAD deficiency in our patient group, a strong case can be made for neonatal screening for MCAD deficiency in the UK.     

Aberrant crypt focus promotion and glucose intolerance: correlation in the rat across diets differing in fat, n-3 fatty acids and energy

McKeown-Eyssen (Cancer Epidemiol. Biomarkers Prevent., 3, 687-695, 1994) and Giovannucci (Cancer Causes Control, 6, 164-179, 1995), noting the striking similarity in lifestyle risk factors for colorectal cancer and insulin resistance, proposed that the hyperinsulinemia, glycemia and hypertriglyceridemia associated with insulin resistance promotes colon cancer. To compare the effect of diet on colon cancer promotion and insulin resistance in the F344 rat, we assessed the effect of fat, n-3 fatty acids and energy in pairwise comparisons on average size of aberrant crypt foci (ACF) and on glucose intolerance in the same animals in a single experiment. Diets high in fat and energy increased and diets with increased n-3 fatty acids and calorie restriction decreased both ACF growth and glucose intolerance compared with control diets. The measures of promotion of colon cancer and insulin resistance were strongly correlated (n = 98, r = 0.67, P < 0.001). In addition, both were highly correlated with daily energy intake (r = 0.62 and 0.66) and were also correlated with basal (post-prandial) insulin, glucose and triglycerides (r = 0.31-0.53, P < 0.01). We concluded that ACF growth and glucose intolerance are correlated for a wide range of diets and that increased circulating energy (glucose and triglycerides) may lead to both colon cancer promotion and insulin resistance.      

Creating a digital radiographic teaching file and database using a PC and common software

OBJECTIVE: We wanted to design an inexpensive, convenient database to store digital radiographic images of multiple formats. CONCLUSION: We designed a database that could be saved in a standard format using readily available software. Users of our database can save images in a Joint Photographic Experts Group (JPEG) format, allowing their easy incorporation into other programs.     

Predictors of operative outcome in patients with human immunodeficiency virus infection and acquired immunodeficiency syndrome

BACKGROUND: Plasma viral load has recently been associated with clinical outcome in patients with human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS). We hypothetized that, in addition to CD4 lymphocytes, plasma HIV-1 RNA counts are predictive of postoperative outcome. METHODS: HIV-infected and AIDS patients admitted to a major teaching hospital requiring invasive or surgical procedures were retrospectively analyzed for postoperative outcome. Preoperative and postoperative immune cell counts including plasma HIV-1 RNA counts were recorded. Chi-square analysis, Fisher's exact test, and multivariate regression were performed with statistical significance P 相似文献   

Interest of free flaps for cranial base reconstruction

We describe our experience in treating 7 patients who underwent skull base reconstruction with free flap (6 latissimus dorsi, 1 rectus abdominis) between October 1996 and November 1998. Four patients underwent temporal bone resection with auricular resection, 2 patients underwent anterior and middle cranial fossa resection, 1 patient underwent frontotemporal resection. There have been no failures of the free flaps and one cerebrospinal fluid leak. We advocate free flap reconstruction after temporal bone resection with auricular resection, and after anterior or middle cranial fossa resection when local flap options are not available or with complex dead space.     

Association of KCNJ11 and ABCC8 single-nucleotide polymorphisms with type 2 diabetes mellitus in a Kinh Vietnamese population

Type 2 diabetes mellitus (T2DM) is a genetically influenced disease, but few studies have been performed to investigate the genetic basis of T2DM in Vietnamese subjects. Thus, the potential associations of KCNJ11 and ABCC8 single nucleotide polymorphisms (SNPs) with T2DM were investigated in a Kinh Vietnamese population. A cross-sectional study consisting of 404 subjects including 202 T2DM cases and 202 non-T2DM controls was designed to examine the potential associations of 4 KCNJ11 and ABCC8 SNPs (rs5219, rs2285676, rs1799859, and rs757110) with T2DM. Genotypes were identified based on restriction fragment length polymorphism and tetra-primer amplification refractory mutation system polymerase chain reaction. After statistically adjusting for age, sex, and BMI, rs5219 was found to be associated with an increased risk of T2DM under 2 inheritance models: codominant (OR = 2.15, 95% confidence intervals [CI] = 1.09–4.22) and recessive (OR = 2.08, 95%CI = 1.09–3.94). On the other hand, rs2285676, rs1799859, and rs757110 were not associated with an increased risk of T2DM. Haplotype analysis elucidated a strong linkage disequilibrium between the 3 SNPs, rs5219, rs2285676, and rs757110. The haplotype rs5219(A)/rs2285676(T)/rs757110(G) was associated with an increased risk of T2DM (OR = 1.42, 95%CI = 1.01–1.99). The results show that rs5219 is a lead candidate SNP associated with an increased risk of developing T2DM in the Kinh Vietnamese population. Further functional characterization is needed to uncover the mechanism underlying the potential genotype-phenotype associations.     

Polyether Ether Ketone Coated with Ultra-Thin Films of Titanium Oxide and Zirconium Oxide Fabricated by DC Magnetron Sputtering for Biomedical Application

Recently, polyether ether ketone has raised increasing interest in research and industry as an alternative material for bone implants. This polymer also has some shortcomings, as it is bioinert and its surface is relatively hydrophobic, causing poor cell adhesion and therefore slow integration with bone tissue. In order to improve biocompatibility, the surface of polyether ether ketone-based implants should be modified. Therefore, polished disc-shaped polyether ether ketone samples were surface-modified by direct current magnetron sputtering with ultrathin titanium and zirconium coatings (thickness < 100 nm). The investigation results show a uniform distribution of both types of coatings on the sample surfaces, where the coatings mostly consist of titanium dioxide and zirconium dioxide. Differential scanning calorimetry revealed that the crystalline structure of the polyether ether ketone substrates was not changed by the coating deposition. Both coatings are amorphous, as shown by X-ray diffraction investigations. The roughness of both coating types increases with increasing coating thickness, which is beneficial for cell colonization. The coatings presented and investigated in this study improve wettability, increasing surface energies, in particular the polar component of the surface energies, which, in turn, are important for cell adhesion.